Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes.

Haibo Tan,Yidan Wang,Weiwei Song,Yunfeng Hou,Qing Song,Tiangang Zhou,Sha Liu,Zhenbo Xu

doi:10.1155/2021/6657476

Haibo Tan, Yidan Wang + Show 6 more

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https://doi.org/10.1155/2021/6657476

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Abstract

Objective It is aimed at investigating the mechanism of palmitic acid (PA) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (nNOS) protein. Methods The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin II-induced hypertensive model rats. The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of Kent Coda, USA. The Ionoptix single-cell contraction detection system was used to detect myocardial cells. ATP level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by Western blot. Results Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; PA increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and PA increased the intracellular ATP level of rats in the sham group but not in the hypertension group. In the hypertension group, the expression of nNOS in the cardiomyocytes was significantly increased, and specific nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was found to restore the positive inotropic effect of PA in the myocardium of the hypertension group. PA was supplemented after using CPT-1 inhibitor etomoxir (ETO); it was found that ETO inhibited the positive inotropic effect of PA on left ventricular cardiomyocytes in the sham group, and PA was supplemented after using SMTC and ETO, it was found that SMTC + ETO could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in myocardium of hypertensive rats. Conclusion PA could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, PA enhanced the contractility of cardiomyocytes by increasing ATP level in them, and the inhibitory effect of PA on myocardial contractility in hypertensive rats may be related to the increased nNOS and CPT-1 in cardiomyocytes.

Highlights

Cardiovascular disease is a serious threat to human health, which accounts for about thirty percent of global deaths
How the contractility of left ventricular cardiomyocytes changed in normal rats with Palmitic acid (PA) supplementation was studied
The expression of neural nitric oxide synthase (nNOS) was inhibited by another nNOS inhibitor L-VNIO, the sarcomere shortening of cardiomyocytes was measured before (0:126 ± 0:003 μm) and after (0:147 ± 0:003 μm) PA administration, and the same results were observed. These results showed that increased nNOS in left ventricular cardiomyocytes under hypertension can reduce the dependence of PA increase in left ventricular cardiomyocytes of hypertensive rats (P < 0:001)

Summary

Introduction

Cardiovascular disease is a serious threat to human health, which accounts for about thirty percent of global deaths. Energy supply to myocardium in healthy adults mainly comes from fatty acid and glucose oxidation. In healthy and hypertensive rat hearts, neural nitric oxide synthase (nNOS) can affect the oxidation of fatty acid in vivo and in vitro. As a synthase of NO, nitric oxide synthase (NOS) is mainly classified into endothelial type (eNOS), neuronal type (nNOS), and inducible type (iNOS). NNOS is the main subtype of NOS, regulating Ca+ in cardiomyocytes of healthy and hypertensive rats and processing Ca+ sensitivity and contractility in myofilaments. The nNOS regulates mitochondrial function and myocardial contractility in both healthy and ischemic hearts. It is unknown whether nNOS is involved in the regulation of the myocardial contractility by the associated fatty acid. Etomoxir (ETO) is the inhibitor of carnitine acyl transferase-1 (CPT-1), which is the speed limit enzyme to fatty acid oxidation, when suppressed, the oxidation of fatty acid decomposition will be weakened

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